DESCRIPTION (provided by investigator): Pelvic inflammatory disease (PID), the frequent infection and inflammation of the female upper genital tract, often results in long-term sequelae, including infertility, chronic pelvic pain, ectopic pregnancy, and recurrent PID. Although Mycoplasma genitalium has recently been recognized as a cause of non-gonococcal, non- chlamydial pelvic inflammatory disease (PID), little is known about the short or long-term consequences. In a recently published study by our group (R01AI067661) that tested women who participated in the PID Evaluation and Clinical Health (PEACH) study for M. genitalium using polymerase chain reaction (PCR), 41 percent of patients with a positive baseline M. genitalium PCR test tested positive again 30 days following treatment for PID. Women testing positive, compared to those testing negative for M. genitalium at baseline were over four times as likely to experience short term treatment failure. Further, we reported that rates of sequelae, including chronic pelvic pain (42 percent), infertility (22 percent), and recurrent PID (31 percent), were distressingly high among women who tested positive for active endometrial M. genitalium infection by PCR at baseline. Although differences in rates of sequelae were not significantly different between women testing positive or negative for M. genitalium, there was a trend toward increased chronic pelvic pain, infertility, and recurrent PID, and decreased pregnancy and live birth following M. genitalium infection. Whereas PCR testing detects the genetic material (DNA) of the M. genitalium bacteria, representing current infection, it cannot determine whether a woman has been previously infected. Thus, we propose a competing renewal of our R01 (R01AI067661) to test for M. genitalium antibodies among stored sera from this same population of patients, allowing us to determine whether or not a woman has ever been infected with M. genitalium. By using this approach, we will be able to estimate cumulative damage to the reproductive tract induced by M. genitalium. We propose to test the hypothesis that women with evidence of prior or current M. genitalium infection, measured by testing antibodies, experience greater gynecologic and reproductive morbidity, as compared to women without serologic evidence of M. genitalium or Chlamydia trachomatis. M. genitalium antibodies will be quantified in already collected and archived sera obtained at baseline and a follow-up visit conducted approximately 5 years post PID among 405 women who participated in the PEACH Study. The aims of our competing renewal are: to evaluate the impact of M. genitalium infection on gynecologic and reproductive morbidity;and to determine if serologic measurement of M. genitalium antibodies (cumulative exposure) better predicts chronic pelvic pain, infertility, and recurrent PID, as compared to a single, current M. genitalium infection measured by PCR. This study, to our knowledge, will be the first to compare the relationships between M. genitalium antibodies and long-term sequelae, including infertility and chronic pelvic pain, following PID. Our study is important, as PID affects more than 1 million women per year and accounts for $9 billion in annual direct and indirect costs. Unfortunately, M. genitalium is not routinely tested for in clinical practice and is resistant to a number of PID treatment regimens, highlighting the importance of this study to raise awareness for the potential need to revise clinical guidelines in order to preserve fertility in patients at risk.